Updated: Apr 3, 2019
Fragile X syndrome is the most common inherited cause of intellectual disability. People with fragile X syndrome often experience difficulties with cognitive processes, such as understanding, memory, thinking and reasoning. However, the cognitive profile within fragile X syndrome is complex because some abilities are better developed, while other abilities are more impaired. Therefore, it is important to better understand these areas of relative strengths and weaknesses, so that supports can be targeted where needed and that the strengths can be built upon.
Fragile X syndrome is characterized by deficits in working memory, which involves the ability to store, manipulate, and retrieve information. However, it is unclear whether the difficulties with working memory in fragile X syndrome are due to a global developmental delay or whether working memory is a specific area of weakness. Working memory is important for learning and social skills. Individuals that have difficulty holding and retrieving information from their memory may also have trouble with skills such as predicting patterns and understanding language. For instance, to have a back and forth conversation with someone, you need to be able to store what the other person said in your short term memory and retrieve information to be able to respond.
Stress can also have a negative influence on memory performance with too much stress resulting in a reduced ability to remember. One way stress can be studied is by investigating how the body responds to the environment. One commonly studied indicator of stress is cortisol: a hormone that is released in stressful situations and signals the body’s “fight or flight” responses. Previous studies have found that individuals with fragile X syndrome have elevated levels of cortisol, suggesting alterations in the way that they are physically responding to stress. However, it is unclear how stress may influence cognitive processes like working memory, in people with fragile X syndrome.
In order to better understand the relationship of stress and cognitive processes in fragile X syndrome, our study aimed to examine the following questions:
Do boys with fragile X syndrome have specific difficulties with working memory tasks?
Do working memory skills change over time in boys with fragile X syndrome?
What is the relationship of cortisol (a physiological indicator of stress) and working memory performance over time in boys with fragile X syndrome?
In order to answer these two questions, the current study included 53 boys with fragile X syndrome and a comparison group of 52 typically developing boys that were matched to the fragile X syndrome sample based on their mental age. Including this comparison group meant that we could see whether any difficulties in the fragile X syndrome group were due to an overall developmental delay (in which case they would perform similarly to those of the same mental age), or a specific area of weakness (in which case they would perform worse).
Two measures of working memory with varying levels of difficulty were used to study working memory performance. The first measure of working memory required the participants to remember a series of words in order. The second was a more complex measure of working memory that required the participants to remember and reorder a series of numbers and objects. Three measures of cortisol were included in the study to assess baseline levels of stress before testing, reactivity or stress after the assessment, and the cortisol change between the start and conclusion of the assessment.
The main findings from this study were that boys with fragile X syndrome had specific deficits in working memory, as they performed worse than the children of a similar mental age on the simpler working memory task. We also found that elevated levels of baseline cortisol in fragile X syndrome were related to more impairment in the memory for words performance over time. Collectively, these results support specific deficits in working memory in fragile X syndrome that are intensified by physiological responses to stress. However, when we examined performance of the more difficult working memory task the boys with fragile X syndrome showed similar improvements in these skills over time to the comparison group.
These results have practical applications and help us understand that cognitive development in fragile X syndrome is influenced by cognitive skills, as well as physiological and emotional processes to stress. In the short term increased levels of arousal (cortisol) help us to manage a perceived stressful situation but if responses to a situation are too high or if levels of arousal remain high for extended periods of time, then it can impair cognitive outcomes, such as working memory.
A better understanding of the cascading effects of how the brain and body’s responses influence development and behaviour is critical to help inform effective interventions and modes of treatment in fragile X and other disorders as well. Our work has shown that increased arousal in fragile X syndrome negatively influences learning and cognitive performance. Therefore, interventions that focus on reducing arousal and stress through the teaching of coping and relaxation skills may help reduce the physiological responses to stress.
Mindfulness-based stress reduction therapies may be alternative avenues to reduce stress and cortisol in fragile X syndrome, in comparison to traditional cognitive behavioural therapies, and should be explored further.
Additionally, clinical and educational professionals working with or testing individuals with fragile X syndrome may want to consider allowing for a “warm-up” period prior to beginning testing to reduce initial reactions to stress and anxiety to the environment or professional.
The use of visual supports and social stories can help prepare individuals with fragile X syndrome to manage stress.
Although none of these suggestions have been explicitly studied or shown to be effective in reducing arousal patterns fragile X syndrome they are implied to be potentially helpful based on the results of the current study.